tbuckley/cabot-search huggingface dataset:
Impact of socioeconomic and medical factors on racial disparities in time to treatment initiation and survival in breast cancer patients.
Authors: Diana Basali, Emily Craig Zabor, Jacob Lindberg, Brittany Peterre, Jacqulyn Tomer, Halle C. F. Moore
Journal: Journal of Clinical Oncology (2022)

e18583 Background: Delays in breast cancer treatment have been associated with adverse outcomes. Previously, we observed longer time to treatment initiation (TTT) and inferior overall survival (OS) among Black versus White patients with breast cancer. We aim to examine the extent to which social, and medical factors influence these outcomes. Methods: Women over age 18 who identified as Black or White and diagnosed with stage I-IV breast cancer between 2015 and 2020 at the Cleveland Clinic were identified. Variables included were age, race, type of insurance, receptor status, hypertension, type 2 diabetes, CKD stage 3/4, obesity, and tobacco use. Characteristics according to race were analyzed by the Chi-squared test for categorical variables and the Wilcoxon rank sum test for continuous variables. The primary outcomes were TTT and OS. TTT was analyzed using multivariable linear regression and OS was analyzed using multivariable Cox regression. Results: Patient characteristics by race are shown in Table. Black patients were older, more frequently had triple-negative (TN) receptor status and comorbidities, and less frequently had private insurance. On multivariable linear regression Black race and increased age were associated with longer TTT (both p &lt; 0.001) whereas TN vs HR+/HER2- was associated with shorter TTT (p = 0.007). On multivariable Cox regression Black race (HR 1.39; p = 0.009), increased age (HR 1.02; p &lt; 0.001), Medicaid/Medicare (HR 1.91) or other insurance (HR 1.68) vs private insurance (p &lt; 0.001), type 2 diabetes (HR 1.55; p = 0.001), CKD stage 3/4 (HR 1.93; p &lt; 0.001), and HER2+ (HR 1.44) or TN (HR 2.41) vs HR+/HER2- (p &lt; 0.001) were associated with increased hazard of death .Obesity (HR 0.73; p &lt;0.025) was associated with decreased hazard of death. Conclusions: Our study highlights racial disparities in breast cancer outcomes including the potential contribution of medical and socioeconomic factors. Further investigation will identify the relative contribution of patient related factors on TTT and OS and explore their impact on breast cancer recurrence. It is critically important for providers to attempt to understand factors contributing to disparities in order to implement interventions that can attempt to limit them.[Table: see text]
Economic evaluations of adjunctive osimertinib treatment in surgically resected epidermal growth factor receptor-positive (EGFR+) non-small cell lung cancer (NSCLC): Analysis for stage 2 disease.
Authors: Briana M Choi, Osama Aqel, Rachel B Abraham, Mavis Obeng-Kusi, Matthias Calamia, Hala Halawah, Ahmad Alamer, Ali McBride, Ivo Abraham, Deniz Tugay
Journal: Journal of Clinical Oncology (2022)

e20506 Background: Following surgical resection, patients with NSCLC require monitoring due to the risk of recurrence. Studies have demonstrated the clinical benefit of osimertinib, a tyrosine kinase inhibitor, as adjunctive therapy in surgically resected EGFR+ NSCLC, including in stage 2 disease. We performed a cost effectiveness/utility analysis of adjunctive osimertinib therapy in stage 2 disease following surgical resection. Methods: A two state partitioned survival model differentiating disease free survival (DFS) from disease recurrence and death was specified (US payer perspective). Parametric functions were fit to digitized overall survival (OS) and DFS curves. A 5 year time horizon was specified, with a 3% discount rate applied to costs and utilities beyond year 1. Costs of treatment (wholesale acquisition cost), adverse events (grade 3/4 except all grades for immunotherapy related AEs), and monitoring were sourced from, respectively, Redbook, literature, and Physician Fee Schedules (US $2021). DFS life years (DFSLY) and quality adjusted life years (DFSQALY), incremental cost effectiveness/utility ratios (ICER/ICUR) in terms of DFSLY and DFSQALY gained (g) were estimated in base case analyses (BSA) and probabilistic sensitivity analyses (PSA). Results: Exponential regression was used to extrapolate osimertinib and placebo Kaplan-Meier curves. As detailed below, in BCA (PSA) the incremental cost of osimertinib over placebo was $778,315 ($778,202). The incremental DFSLY was 1.740 (1.738), which yielded ICER of $447,349/DFSLYg ($447,768/DFSLYg). The incremental DFS QALY was 1.234 (1.232), yielding ICUR of $630,910/DFSQALYg ($631,498/DFSQALYg). Conclusions: As to disease recurrence in stage 2 surgically resected EGFR+ NSCLC, our model associated adjunctive osimertinib therapy with incremental clinical gains of 1.740 (1.738) DFSLY and 1.234 (1.232) DFSQALY compared to placebo, however at marked incremental cost. As adjunctive osimertinib treatment is indicated in EGFR+ NSCLC disease stages 1B and 3A, the present stage 2 cost effectiveness/utility results should be compared to those for stages 1B and 3A.[Table: see text]
Molecular phenotypes of colorectal cancer.
Authors: Tatiana Krashikhina
Journal: Journal of Clinical Oncology (2022)

e15506 Background: Despite the positive results of colorectal cancer treatment, there is a group of patients that progresses despite successful treatment for I–II stage of the disease. it may be that modern predictors in do not fully cover the entire spectrum of molecular genetic traits, especially the tumor microenvironment. Perhaps expression analysis is not only tumor tissue, but resection margin could also reach a consensus on the molecular gene phenotypes of colorectal cancer with the achievement of the goal of prognostic efficiency and therapeutic and prophylactic diagnostic tactics. Methods: The expression level of 64 genes in tumor tissue in samples obtained from 172 patients with stage I–III CRC was analyzed by real-time Polymerase chain reaction (PCR). The mean follow-up time was 28.15±14.7 months. Data analysis and predictive modeling arrays using the R 3.6.3 Computation Evaluation Framework (R Foundation for statistical computing, Vienna, Austria) using additional packages rms 5.1-4, survival 3.2-7 and pROC 1.16.2. Results: As a result of statistical analysis, data were obtained on the presence of predictors of the studied unfavorable source code among the selected sets of genes carcinogenesis in colorectal cancer. The next step revealed progression status with BIRC5, IL2, SCUBE2, MYC and P16INK4A gene expression as in tissues tumors, and in resection margin. 2 regression models were built to predict survival without progression in patients with the inclusion of the level of expression in the tumor tissue- nor, the inclusion of the level of gene expression in tumor and resection margin. Model with inclusion only tumor transcripts statistics did not differ from models without predictors. Conclusions: In this study, it was possible to identify a group of genes associated with certain favorable prognosis and responsible in one way or another for proliferation, angiogenesis, immune status of the tumor. It can be concluded that the study of the level of expression of numerical genes in tumor tissue can become a promising direction for the selection of patients in the group of poor prognosis in colorectal cancer.
Pharmacogenomic prediction of immune-related adverse events from immune checkpoint inhibitors among Asian patients.
Authors: Yiqing Huang, Folefac Aminkeng, Alvin S.C. Wong, Sen Hee Tay, Joseph J Zhao, Yvonne Ang, Ross A. Soo, Boon Cher Goh
Journal: Journal of Clinical Oncology (2022)

2547 Background: Immune checkpoint inhibitors (ICIs) have ushered in a unique entity known as immune-related adverse events (IrAEs) that can be debilitating and challenging for physicians. Given that genomic variation underlies both disease susceptibility and drug response, there is reasonable cause to believe that genomic markers are predictive of IrAEs. We perform a pioneering pharmacogenomic study to uncover genomic biomarkers associated with IrAEs from ICIs. Methods: Since March 2018, we recruited cancer patients treated with ICIs from the National University Cancer Institute Singapore and Tan Tock Seng Hospital. IrAEs were clinical characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. DNA was extracted and genotyped by Infinium Global Screening Array (700K markers). Statistical analyses were performed using SVS/HelixTree. Genetic association was performed by logistic regression. Bonferroni corrected P &lt; 7.1E-08 was considered statistically significant. Results: We conducted a pilot pharmacogenomic genome-wide association study (GWAS) on 307 patients of Asian Ancestry. Median age was 62. Majority were male (68.1%), Chinese (75.9%), ECOG PS 0-1 (91.6%), stage IV cancer at diagnosis (64.6%). Non-small cell lung cancer (36.2%), renal cell carcinoma (12.4%) and hepatocellular carcinoma (7.2%) were the three most common cancers. Top four ICIs used were pembrolizumab, nivolumab, atezolizumab and durvalumab, respectively (44.6%, 26.1%, 10.1% and 10.1% respectively). Nine percent of patients received dual ICIs concurrently. Median duration of treatment was 152 days and median follow up was 212 days. IrAEs were seen in 50.5% of patients. Skin (21.8%), endocrine (6.8%) and hepatotoxicity (5.9%) were the most common IrAEs. Eight percent of patients had CTCAEv5 grade ≥3 toxicity, of which hepatotoxicity (2.6%), skin (1.6%) and pulmonary toxicities (1.3%) were the most common. A preliminary pharmacogenomic investigation revealed one potential novel genetic locus associated with IrAEs: LOC105373202 rs5915369; Unadjusted P= 6.6E-08, OR (95%CI) = 27.8 (3.7-206.5), minor allele = A, 10.7% in cases vs 0.4% in controls. We also identified an additional 3 independent SNPs (rs167609, rs2341687, DMDrs5928214) with nominal significance (7.1E-0-8≤ P&lt; 5.0E-7). Conclusions: This pilot pharmacogenomics GWAS uncovered 4 potential novel genetic loci predictive of IrAEs from ICIs amongst Asian patients. Further pharmacogenomic discovery/replication and functional validation studies are currently on-ongoing to identify specific genomic biomarkers that predispose individual patients to IrAEs.
Impact of systemic therapy regimen on survival of PCNSL.
Authors: James Janopaul-Naylor, Alfredo Daniel Voloschin, Jimmy S Patel, Manali Rupji, Kimberly B. Hoang, Jeffrey J. Olson, Hui-Kuo George Shu, Jim Zhong, Stewart G. Neill, Bree R. Eaton
Journal: Journal of Clinical Oncology (2022)

2070 Background: Primary CNS Lymphoma (PCNSL) is a rare and often fatal disease. Treatment includes multi-agent systemic therapy with a backbone of high-dose methotrexate (HD-MTX). Despite multiple drug and radiotherapy combinations for induction and consolidation treatment there remains no clear standard of care. The purpose of this analysis is to evaluate how varying treatment approaches impacted clinical outcomes at our institution. Methods: Data retrospectively collected for 95 consecutive patients with PCNSL pathologically confirmed from 2002 to 2021. Primary endpoint was OS with secondary endpoints of PFS and LC. Progression based on RANO criteria. Kaplan-Meier analyses, Log-rank test and Cox proportional hazard models used for time to event endpoints. MVA by backward selection applying an alpha of 0.2 for associations with 1 st line chemo agents, number of cycles of HD-MTX (&gt;6 or 0-5), size of enhancing tumor at presentation, CSF cytology, type of surgery (biopsy, STR, or GTR), and use of WBRT. Results: Most patients had KPS &gt;70 (64.2%), were HIV negative (89.5%), and had no history of solid organ transplant (95.8%). Diagnosis was made by biopsy (73.7%) or resection (GTR 13.7%, STR 12.6%). 54.3% had &lt;14 cc contrast-enhancing tumor volume (median 12.6 cc, range 0.5 - 67.8 cc) and 48.6% had single enhancing lesion. Of the 62 patients treated first line with at least 1 cycle of HD-MTX, 61.3% were treated with HD-MTX + Rituximab (R) and 33.9% with HD-MTX + R + temozolomide (TMZ). With or after induction HD-MTX, 1-3 patients received one or a combination of cytarabine, thiotepa, procarbazine, vincristine, carmustine, or ASCT. Of the 60 patients with evaluable CSF, 30.0% had positive cytology. IT chemotherapy (ITc) was administered to 12 patients (5 with + cytology, 4 with - cytology, 3 with unknown cytology). WBRT for consolidation after chemotherapy used for 3 patients and as monotherapy for 9 patients. 2-year OS and PFS rate was 50.1% (95% CI 38.6%-60.5%) and 38.5% (95% CI 27.9%-49.0%). On MVA, &gt; 6 cycles of MTX was associated with superior OS, PFS, and LC. For patients receiving any chemotherapy, addition of R was associated with inferior OS while ITc was associated with improved OS, PFS, and LC (Table). There was no OS association on MVA with TMZ, GTR, consolidation WBRT, or size or number of initial lesions (p&gt;0.05). Conclusions: Completion of induction HD-MTX and use of ITc was associated with better outcomes in this population. Incorporation of R into 1 st line therapy was associated with worse OS. Survival remained poor throughout the study period, underscoring importance of further innovation. [Table: see text]
Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results.
Authors: David Andrew Sallman, Monzr M. Al Malki, Adam Steven Asch, Eunice S. Wang, Joseph G. Jurcic, Terrence J. Bradley, Ian W. Flinn, Daniel Aaron Pollyea, Suman Kambhampati, Tiffany N. Tanaka, Joshua F. Zeidner, Guillermo Garcia-Manero, Deepa Jeyakumar, Lin Gu, Anderson Tan, Mark Chao, Carol Elaine O'Hear, Indu Lal, Paresh Vyas, Naval Guastad Daver
Journal: Journal of Clinical Oncology (2022)

7017 Background: Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal overexpressed on cancer cells. CD47 blockade by magrolimab induces macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine (AZA) via upregulation of “eat me” signals. Here we report final Phase 1b data in patients (pts) with untreated HR-MDS (NCT03248479). Methods: Pts with previously untreated intermediate-/high-/very high-risk MDS per IPSS-R received magrolimab IV as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg weekly or Q2W maintenance dose. AZA 75 mg/m 2 was administered IV or SC on Days 1–7 of each 28-day cycle. Primary endpoints were safety/tolerability and complete remission (CR) rate. Results: 95 pts (median age 69 years [range 28, 91]) were treated. IPSS-R risk was intermediate, high, or very high in 27%, 52%, and 21%, respectively. MDS was therapy-related in 22%; 26% (n=25) had a TP53 mutation and 62% had poor-risk cytogenetics (27% complex). Median (range) number of cycles was 6 (1, 27). The most common TEAEs included constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (44%). The most common Grade 3/4 TEAEs included anemia (47%), neutropenia (46%), thrombocytopenia (46%), and WBC count decreased (30%). 6 pts discontinued treatment due to AEs. 60-day mortality was 2%. Median Hb change from baseline (BL) at first post-dose sample was –0.7 g/dL (range –3.1, +2.4). CR and objective response (OR) rates were 33% and 75% with 31% of evaluable OR pts with abnormal cytogenetics at BL having cytogenetic CR. Median time to first OR, duration of CR (DCR), duration of OR, and PFS were 1.9, 11.1, 9.8, and 11.6 mos. OS rates at 12 and 24 mos were 75% and 52%, respectively (median NR with 17.1 mos follow-up for OS). For patients evaluated with sequential WES with a VAF cutoff of 5%, 3 of 3 pts with TP53 mutation who achieved CR had TP53 VAF &lt;5% by C5D1. Favorable outcomes were observed in both TP53 mutant (40% CR, median OS 16.3 months) and wildtype pts (31% CR, median OS NR; Table). Conclusions: Magrolimab+AZA was well tolerated with promising efficacy in pts with untreated HR-MDS including those with TP53-mut and TP53-wt disease. A Phase 3 trial of magrolimab/placebo+AZA (ENHANCE: NCT04313881) is ongoing. Clinical trial information: NCT03248479. [Table: see text]
Which patients are at risk for poorer outcomes from testicular cancer (TC) and its treatment?
Authors: Linda A. Jacobs, David J. Vaughn, Abigail N. Blauch, Donna A. Pucci, Steven C Palmer
Journal: Journal of Clinical Oncology (2022)

e24060 Background: TC is a highly treatable disease with a 5-year combined relative survival rate of 95%. Survival, however, can come at a price, and longer-term negative physical and psychosocial sequelae have been described in the literature. We examined unmet needs and psychological and physical well-being in a sample of TC survivors attending a survivorship visit with the aim of describing the outcomes achieved and identifying characteristics of individuals most at risk of poor outcomes. Methods: Patients attending a survivorship clinic visit completed measures assessing 13 common physical and psychosocial needs, anxiety and depression (HADS), and QoL (SF-12V2). These data were described, subjected to hierarchical cluster analysis, and the resulting clusters were examined for disease, treatment, and demographic differences. Results: Participants (N = 312) from the same institution were primarily white (94%), non-Hispanic (98%), middle-aged (M = 42.8, SD = 11.1), married (74%), college graduates (79%), making more than $80,000/year (72%). On average, participants were diagnosed 9.8 (SD = 6.5) years earlier, though that ranged from 2-44 years, with Stage I or II TC (80%) that required surgery (99%) including RPLND (22%), chemotherapy (50%), and/or radiation (12%). Unmet needs were generally low (M = 0.91, SD = 2.1, R = 0-13) with 72% reporting no unmet need, and no unmet need was endorsed at a rate higher than 10%. Depressive symptoms were uncommon (HADS-D M = 2.3 SD = 2.6) with 95% classified as having no depressive symptoms. Symptoms of anxiety were more common (HADS-A M = 4.9; SD = 3.7) although 78% were classified as having no symptoms. QoL was similar to population norm values (M = 50) for both mental (M = 51.8) and physical (M = 51.7) well-being. Hierarchical cluster analysis of unmet needs, anxiety and depressive symptoms, and QoL revealed 2 distinct groups, one (86%) experiencing more positive outcomes than the other (14%). These groups differed significantly in unmet needs (M's 0.5 vs. 3.3), anxiety (M's 3.9 vs. 10.6) and depressive symptoms (M's 1.6 vs. 6.3), and mental QoL (M's 54.4 vs. 34.3; all p's &lt; 0.001). Groups did not differ with respect to physical well-being (M's 51.4 vs. 53.2, ns). Individuals in the less well-functioning group were more likely to have been diagnosed with Stage 3 disease, be unmarried, and have a lower income (all p &lt; 0.05). Treatment intensity, educational attainment, age, and time from diagnosis were not significantly associated with group membership. Conclusions: Most TC survivors report good functioning with few unmet needs and low levels of anxiety and depression during survivorship. A minority of TC survivors, however, experience substantially greater psychosocial but not physical difficulties, and these individuals are likely to be unmarried, have lower income, and been initially diagnosed with more advanced disease.
Clinical outcomes and safety of enzalutamide (ENZA) plus androgen-deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) in patients aged &lt; 75 and ≥ 75 years: ARCHES post hoc analysis.
Authors: Russell Zelig Szmulewitz, Jeffrey Holzbeierlein, Arun Azad, Taro Iguchi, Arnauld Villers, Antonio Alcaraz, Boris Alekseev, Neal D. Shore, Brad Rosbrook, Fabian Zohren, Jie Ma, Gabriel P. Haas, Francisco Gomez-Veiga, Arnulf Stenzl, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2022)

5069 Background: Patients with metastatic prostate cancer aged ≥75 years have a poorer prognosis compared with younger patients. In ARCHES (NCT02677896), ENZA + ADT improved radiographic progression-free survival (rPFS), overall survival (OS), and other key secondary endpoints vs. placebo (PBO) + ADT in patients with mHSPC. Final OS results confirmed a long-term survival benefit with ENZA + ADT. This post hoc analysis of ARCHES data investigated OS and other clinical outcomes in patients aged &lt;75 and ≥75 years. Methods: Patients with mHSPC (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel use. Subgroup analysis was performed in patients aged &lt;75 and ≥75 years. Efficacy and safety outcomes were compared across treatment arms. Results: Of the ARCHES population, 339 patients (29.5%) were aged ≥75 years (ENZA + ADT, n=170; PBO + ADT, n=169); PBO patients crossing over to ENZA were aged: &lt;75 years, n=133; ≥75 years, n=47. Some differences in baseline characteristics were observed between age groups, such as higher prior docetaxel use in patients aged &lt;75 years (ENZA + ADT, 21.0%; PBO + ADT, 20.4%) vs. those aged ≥75 years (ENZA + ADT, 10.6%; PBO + ADT, 11.2%). When compared to PBO + ADT, ENZA + ADT improved OS and other secondary efficacy endpoints in both age groups without evidence of statistical heterogeneity (Table); however, 95% confidence intervals for OS and rPFS hazard ratios spanned 1 in the older age group. The safety profile of treatment arms was generally similar in both age groups, with a higher incidence of falls, cognitive impairment, and cardiovascular events among elderly patients receiving ENZA + ADT vs. PBO + ADT. Conclusions: This post hoc analysis of ARCHES data demonstrated that ENZA + ADT provides clinical benefit and is generally well-tolerated in patients with mHSPC aged ≥75 years, supporting the therapeutic role of ENZA in these patients. Clinical trial information: NCT02677896. [Table: see text]